Methods and system for performing remote ischemic preconditioning

ABSTRACT

A system for remote ischemic preconditioning that includes a cuff, and actuator, and a controller that operates the actuator according to a treatment protocol. The treatment protocol includes a plurality of treatment cycles that each comprise cuff actuation, an ischemic duration, cuff release, and a reperfusion duration.

RELATED APPLICATIONS

This application is a continuation of and claims priority to U.S.application Ser. No. 11/634,749, filed Dec. 6, 2006, which is herebyincorporated by reference in its entirety.

FIELD

The invention relates to systems for performing remote ischemicpreconditioning.

DISCUSSION OF RELATED ART

Ischemic diseases are significant causes of mortality in industrializednations. It is well established that tissue damage results from ischemia(stoppage of blood flow to the tissue) followed by reperfusion (reflowof blood to the tissue). Ischemia and reperfusion causes disturbance ofmicrocirculation with ensuing tissue damage and organ dysfunction.Organs such as the kidney, heart, liver, pancreas, lung, brain andintestine are known to sustain damage following ischemia andreperfusion.

In ischemic preconditioning (IPC), a portion of a subject's body issubjected to brief ischemic episodes, which have been found to rendertissue resistant to injuries during subsequent ischemic episodes. Thephenomenon of ischemic preconditioning, first described by Murry et al.,has been demonstrated in most mammalian tissues. IPC is now recognizedas one of the most potent, innate, protective mechanisms againstischemia reperfusion (I-R) injury. Despite the profound protectiveeffects demonstrable in experimental models, there are relatively fewclinical reports of its effectiveness. This is, at least in part,related to the difficulty in rendering the target organ transientlyischemic prior to an intervention and the method of inducing IPC mayitself induce tissue dysfunction.

Remote ischemic preconditioning (rIPC) refers to the deliberateinduction of transient ischemia in a subject at a position remote fromat least some of the tissue to be protected. Often, rIPC includesinducing transient ischemia at a subject's limb, to protect organsremote from the limb. Remote ischemic preconditioning (rIPC) was firstdescribed by Przyklenk et al. in 1993. They showed that transientischemia in the circumflex coronary artery territory rendered remotemyocardium resistant to injury following prolonged ischemia in the leftanterior coronary artery territory. Myocardial protection has beendemonstrated by a variety of remote stimuli; including renal ischemia,liver ischemia, mesenteric artery ischemia, and skeletal muscle hindlimb ischemia.

Remote ischemic preconditioning has been carried out with asphygnamometer—an instrument typically used to measure a subject's bloodpressure. The cuff of the sphygnamometer is placed about the subject'sarm and is inflated to a pressure great enough to occlude blood flowthrough the arm (i.e., pressure greater than the subject's systolicblood pressure). The cuff is maintained in the inflated state to preventblood flow through the limb for a doctor-specified period of time,referred to herein as the ischemic duration. After the ischemicduration, pressure is released from the cuff to allow reperfusion ofblood through the limb for a period of time that is referred herein asthe reperfusion duration. The cuff is then re-inflated and the procedureis immediately repeated a number of times specified by a doctor.

Using a sphygnamometer or other manual type tourniquet to perform rIPCcan pose some difficulties. Such approaches typically require a doctor,nurse, or other medical professional to perform the procedure. Moreover,the doctor or nurse is required to remain present during the entireremote ischemic preconditioning procedure, which may extend upwards ofan hour or more. Remote ischemic preconditioning protocols may varyextensively from subject to subject or even from treatment to treatmentfor a given subject, which may cause confusion among those thatadminister the treatment.

Blood pressure measurement systems exist; however, such systems areinadequate for performing rIPC, for at least several reasons. Thesystems are not configured to hold pressure about a subject's limb foran extended duration and cannot cycle between ischemic and reperfusiondurations as may be required when remote ischemic preconditioning isperformed on subjects. As such, blood pressure measuring systems wouldstill require the presence of a medical professional if used for rIPC tomonitor or otherwise restart the blood pressure measurement process forevery cycle necessary during the entire rIPC treatment.

Systems also exist for occluding blood flow through a subject's limbduring surgery, so as to create a bloodless operating field. PCTpublication WO 83/00995 describes one such system. The system maintainscuff pressure at a set point above systolic pressure, but lacks anycontrols for releasing the cuff and re-inflating the cuff in a mannersufficient for rIPC.

Other systems have been used to produce external counter-pulsation bloodflow in a subject. US Patent Application 2006-0058717 describes such asystem. In external counterpulsation treatment, a series of pneumaticcuffs are wrapped about a subject's limbs and are inflated and deflatedin a manner that creates a pressure wave which increases bloodflow tothe subject's heart. The inflation and deflation cycles are timed to thesubject's heart beat, instead of longer durations typically used inrIPC. In this regard, external counterpulsation treatment systems areinadequate for performing (rIPC).

The applicants have identified that there is a need for providing asystem to perform rIPC without requiring the constant presence of amedical professional.

SUMMARY

According to one aspect of the invention, a system for remote ischemicpreconditioning is disclosed. The system comprises a cuff configured tocontract about a limb of a subject. An actuator is connected to the cuffand, when actuated, causes the cuff to contract about the limb of thesubject to reduce blood flow through the limb. A controller controls theactuator according to a treatment protocol that includes a plurality oftreatment cycles. Each treatment cycle comprises cuff actuation, duringwhich the actuator contracts the cuff about the limb of the subject to apressure above systolic pressure to occlude blood flow through the limband an ischemic duration, during which the actuator maintains the cuffcontracted about the limb at a set point above systolic pressure toocclude blood flow through the limb. The ischemic duration lasts for atleast five seconds. Each treatment cycle also comprises cuff release,during which the actuator releases the cuff to allow blood flow throughthe limb, and a reperfusion duration, during which the cuff ismaintained about the limb in a relaxed state to allow blood flow throughthe limb. The reperfusion duration lasts for at least a minute or so.

Various embodiments of the present invention provide certain advantages.Not all embodiments of the invention share the same advantages and thosethat do may not share them under all circumstances.

Further features and advantages of the present invention, as well as thestructure of various embodiments of the present invention are describedin detail below with reference to the accompanying drawings.

BRIEF DESCRIPTION OF THE FIGURES

The accompanying drawings are not intended to be drawn to scale. In thedrawings, each identical or nearly identical component that isillustrated in various figures is represented by a like numeral. Forpurposes of clarity, not every component may be labeled in everydrawing.

Various embodiments of the invention will now be described, by way ofexample, with reference to the accompanying drawings, in which:

FIG. 1 is a schematic representation of one embodiment of a remoteischemic preconditioning system, including a pneumatically inflatablecuff configured to contract about the limb of a subject.

FIG. 2 is a block diagram of one embodiment of an operating scheme ofthe rIPC system.

FIG. 3 shows an alternate embodiment of a cuff configured to contractabout the limb of a subject.

DETAILED DESCRIPTION

Aspects of the invention relate to a system that can provide can providea safe and reliable method of performing remote ischemic preconditioningThe system is capable of executing a treatment protocol that has beendefined by a medical professional, with minimal or no oversight by themedical professional. Embodiments of the system include features tosafeguard the subject and to monitor compliance with a treatmentprotocol.

The overall system, as exemplified in FIG. 1, includes a cuff 10, anactuator 12, a controller 14 and a user interface 16. The cuff isconfigured to be placed about the limb 15 of a subject, such as an armor leg of the subject. The actuator, when actuated, causes the cuff toretract about the limb to occlude bloodflow through the limb. Thecontroller executes a treatment protocol that comprises repeating atreatment cycle one or more times. The treatment cycle itself includes:actuating the cuff to prevent bloodflow, maintaining the cuff in anactuated state for an ischemic duration, releasing the cuff, andmaintaining the cuff in a relaxed state to allow reperfusion.

FIG. 2 shows a block diagram that represents an operating scheme thatmay be used to perform rIPC, according to one illustrative embodiment ofthe invention. The scheme begins with placement of a cuff about asubject's limb. The system is then activated and the treatment protocolis initiated through the controller. In one embodiment, the system isactivated by a medical professional. In another embodiment, the systemmay be activated by the subject himself or herself. The cuff contractsto apply an initial pressure, greater than systolic pressure, to thesubject's limb. As discussed herein, the initial pressure may be adefault value of the system or may be programmed into a particulartreatment protocol. The cuff then deflates to identify the subject'ssystolic pressure by monitoring the subject for the onset of Korotkoffsounds or vibrations. Once systolic pressure has been identified, thesystem initiates the first treatment cycle of the treatment protocol. Insome embodiments, systolic pressure may be identified as an initialportion of the treatment protocol.

The treatment cycle begins as the cuff contracts to apply a targetpressure, greater than the subject's systolic pressure by an amountdefined in the treatment protocol, to the subject's limb. This occludesblood flow through the subject's limb. The external pressure against thesubject's limb is held for an ischemic duration defined in the treatmentprotocol. The system monitors the subject during the ischemic durationfor pressure release criteria, which may include system power failure,system power spikes, and manual activation of quick release mechanism.The system also monitors the subject during the ischemic duration forany signs of reperfusion through the subject's limb, and accordingly,increases the external pressure applied by the cuff to prevent suchreperfusion. Signs of reperfusion can include the onset of Korotkoffsounds or vibrations. After passage of the ischemic duration, the cuffreleases pressure from about the subject's limb to allow reperfusion.Reperfusion is allowed for a reperfusion duration defined in thetreatment cycle.

The initial treatment cycle may conclude with the passage of thereperfusion duration. At this time, a subsequent treatment cycle maybegin as the cuff is actuated to contract about the subject's limb toocclude blood flow through the limb for another ischemic duration. Datacollected during the prior treatment cycle may be recorded for any oneor more of a variety of reasons, including but not limited to, aiding amedical professional with determining the extent of the subject'scompliance with the treatment protocol, logging blood pressure data,aiding with medical research, and the like.

The cuff illustrated in FIG. 1 is configured to be positioned about thelimb of a subject and to contract about the limb when actuated. In oneembodiment, the sleeve is wrapped about a subject's upper arm, calf, orthigh and is fastened snuggly in place. Portions of the cuff may includehook and loop type material that can be used to fasten the sleeve inplace about the subject's limb. The actuator inflates the cuff such thatthe limb is constricted to the point of occluding blood flow through thesubject's limb.

The illustrated cuff includes an inflatable bladder (not shown) thatreceives a fluid, such as air, to cause the cuff expand and retractabout a subject's limb. The bladder is constructed of an air impermeablematerial, such as flexible plastic or rubber. A connection port 18 ispresent at one end of the bladder to allow air to enter the bladderduring inflation, or to exit the bladder during deflation. The port mayinclude engagement features to facilitate a connection to the actuator,such as by an air hose. These features may include threads, clips, andthe like. Although the illustrated embodiment includes a single bladderpositioned within a cuff, it is to be appreciated that other embodimentsare also possible. By way of example, according to some embodiments, thefabric sleeve may itself be air impermeable, such that no separatebladder is required. In other embodiments, multiple, separate inflatablebladders may be incorporated into a common sleeve, as aspects of thepresent invention are not limited in this respect.

The general size of subjects that undergo rIPC treatment may varygreatly, from sizes associated with neonatal infants to those associatedwith obese adults. Given this variance, it may be desirable for someembodiments of cuffs to be adjustable over a wide range to accommodatethe variety of subject limb girths that may be expected. According tosome embodiments, the cuff comprises an inflatable fabric sleeve havinga length greater than three feet, such that a girth of up to three feetmay be accommodated. Embodiments of cuffs may include a width as smallas two inches, one inch, or even smaller, so as to accommodate the upperarm or leg of a much smaller subject, including a neonatal infant. It isto be appreciated, however, that other embodiments may be configured toencircle a much smaller range of limb sizes, as aspects of the presentinvention are not limited in this regard.

Various devices may be used as an actuator to constrict the cuff about asubject's limb, or to release the cuff. As illustrated in embodiment ofFIG. 1, the actuator includes a pneumatic pump to provide pressurizedair to an inflatable cuff through an air hose. The actuator alsoincludes a release valve 20 that, when actuated, opens a passagewaybetween the inflatable cuff and the external environment to allowpressurized air to escape from the cuff, so that the cuff loosens aboutthe subject's limb.

The air pump can comprise any device capable of delivering compressedair. According to some embodiments, the air pump includes a pistoncompressor, although other types of pumps, like centrifugal pumps andscroll compressor may also be used. The pump may be configured toprovide air flow at a rate of between 0.1 to 20 cubic feet per minute,with a head pressure of up to 50 psi, according to some embodiments.However, other flow rates and/or pressures are possible, as aspects ofthe invention are not limited in this respect.

As discussed above, the actuator may also include a release mechanism torelease a cuff from about the subject's limb. In the illustratedembodiment, the release comprises a release valve 20 that is positionedwithin the controller housing. The release valve, as shown, may be asolenoid operated and can move rapidly between fully closed and fullyopen positions to rapidly release air from the cuff and, in turn, torapidly release the cuff from a subject. According to some embodiments,the same release valve or another release valve may also be actuated toopen slowly, such as to adjust the pressure of the cuff or to allow amore controlled release of pressure such as may be required when thesubject's blood pressure is measured.

Embodiments of the system may include safety features to allow rapidrelease of the cuff from a subject's limb. Moreover, some of theseembodiments may be readily activated by a subject, such as when thesubject feels discomfort. In one embodiment, the safety release 22includes a large button positioned on or near the cuff. In this regard,the safety release is within reach of the subject. In other embodiments,the safety release may comprise a separate actuator, such as one thatmay be held in the free hand of the subject. Activating the safetyrelease may cause the release valve of a pneumatic cuff to open, therebyallowing rapid removal of air from the cuff.

The system may also include a continually operating, cuff releasemechanism. By way of example, a slow release valve may be incorporatedinto a pneumatic cuff to provide for a continual, slow release ofpressurized air from the cuff. The continual slow release mechanism mayprovide for the safe release of a subject's limb, even in the face ofpower failures or other events that may prevent redundant safetyfeatures from operating properly. Similar type mechanism may beincorporated into embodiments that do not utilize a pneumaticallyinflatable cuff, as continual slow release mechanisms are not limited topneumatic cuffs.

Embodiments of the system include a controller that receives informationfrom a treatment protocol and any other sensors in the system to, inturn, control the actuator to perform remote ischemic preconditioning.The controller and treatment protocol combination may be implemented inany of numerous ways. For example, in one embodiment the controller andtreatment protocol combination may be implemented using hardware,software or a combination thereof. When implemented in software, thesoftware code can be executed on any suitable processor or collection ofprocessors, whether provided in a single computer or distributed amongmultiple computers. It should be appreciated that any component orcollection of components that perform the functions described herein canbe generically considered as one or more controllers that control thefunctions discussed herein. The one or more controllers can beimplemented in numerous ways, such as with dedicated hardware, or withgeneral purpose hardware (e.g., one or more processors) that isprogrammed using microcode or software to perform the functions recitedabove. The one or more controllers may be included in one or more hostcomputers, one or more storage systems, or any other type of computerthat may include one or more storage devices coupled to the one or morecontrollers. In one embodiment, the controller includes a communicationlink to communicate wirelessly, or via electrical or optical cable, to aremote location.

In this respect, it should be appreciated that one implementation of theembodiments of the present invention comprises at least onecomputer-readable medium (e.g., a computer memory, a floppy disk, acompact disk, a tape, etc.) encoded with a treatment protocol in theform of a computer program (i.e., a plurality of instructions), which,when executed by the controller, performs the herein-discussed functionsof the embodiments of the present invention. The computer-readablemedium can be transportable such that the treatment protocol storedthereon can be loaded onto any computer system resource to implement theaspects of the present invention discussed herein. In addition, itshould be appreciated that the reference to a treatment protocol orcontroller which, when executed, performs the herein-discussedfunctions, is not limited to an application program running on a hostcomputer. Rather, the term treatment protocol is used herein in ageneric sense to reference any type of computer code (e.g., software ormicrocode) that can be employed to program a processor to implement theherein-discussed aspects of the present invention.

The system may also comprise one or more sensors 26 that receiveinformation from the subject and/or portions of the system itself. Suchsensors may receive information regarding blood flow in any portion ofthe subject, including the limb that is being treated. These sensors mayalso receive information regarding other operating parameters of thesystem, such as air pressure within a pneumatic cuff, direct readings ofpressure applied by cuff, or tension within portions of a tension band.

Pneumatic cuffs may include a sensor to measure pressure within thecuff. Cuff pressure is often directly indicative of the pressure thatexists within a blood vessel of the limb beneath the cuff. Thecontroller of a system is often programmed to target a particular cuffpressure that is to be maintained during the ischemic duration of atreatment cycle, as is discussed herein. In embodiments that include apneumatic cuff, the pressure sensor may be positioned anywhere withinthe pressurized space of the cuff, the air hose, or even within theactuator itself. Pressure sensors may also be positioned on an innersurface of the cuff to directly measure the pressure between the cuffand an outer surface of the subject's limb. In use, the cuff may beoriented such that the pressure sensor is positioned directly above thesubject's artery, so as to provide a more direct measurement of pressureat a blood vessel of interest.

In one embodiment, systems may also include one or more vibration and/orultrasonic sensors 28 to identify Korotkoff sounds. Korotkoff sounds aregenerally understood to be present when pressures between systolic anddiastolic are externally applied to the artery of a subject. Systolicpressure is associated with a pressure value that completely occludesblood flow through a subject's blood vessels, and in this regard, may beused by the system as feedback to identify when pressure in the systemis low enough to allow blood flow, or high enough to occlude blood flow.

One or more sensors may be included to confirm the cessation of bloodflow or reperfusion in the limb that receives the cuff For instance, insome embodiments, a pulse oximeter 30 may be positioned on a distalportion of the limb that receives the cuff, such as on a finger or toeof the limb. The pulse oximeter can provide information regarding bloodpulsing through the subject's blood vessels and the percentage ofhaemoglobin that is saturated with oxygen. The pulse oximeter willdetect an absence of pulses when blood flow though a limb is notoccurring to confirm the occlusion of blood flow. Moreover, the pulseoximeter may also detect the percentage of haemoglobin saturated withoxygen, which will drop as blood flow through the limb ceases. It is tobe appreciated that other sensors may also be used to confirm thecessation of blood flow, such as a photoplethysmographic transducer, anultrasonic flow transducer, a temperature transducer, an infrareddetector, and a near infrared transducer, as aspects of the inventionare not limited in this respect.

As mentioned above, the system includes a treatment protocol that,through the controller, directs the operation of the system. Embodimentsof the treatment protocol include a treatment cycle that comprises cuffactuation, an ischemic duration, cuff release, and a reperfusionduration. In many embodiments of treatment protocols, the treatmentcycle may be repeated multiple times. Additionally, some embodiments ofthe treatment protocol include systolic pressure identification.

The cuff actuation portion of the treatment cycle comprises contractingthe cuff about the limb of a subject to occlude blood flow through thelimb. Contraction of the cuff is accomplished by the controller readinginstructions from the treatment protocol, such as a target set point forcuff pressure, and then by the initiating the controller to bring thecuff to the target set point. Attainment of the target set point may besensed through any of the herein described sensors and techniques.

During the ischemic phase of the treatment cycle, pressure is maintainedabout the subject's limb to prevent reperfusion of blood flow throughthe limb. The length of the ischemic phase, termed the ischemicduration, is typically defined by a doctor, or other medicalprofessional, and is programmed into the treatment protocol. Ischemicduration may be as short as a few seconds, or as long as 20 minutes, oreven longer, as aspects of the invention are not limited in this regard.In some embodiments, the ischemic duration varies from treatment cycleto treatment cycle during the same treatment protocol, although in otherembodiments, the ischemic duration remains constant.

The controller acts to maintain pressure, applied by the cuff, at a setpoint above the subject's systolic pressure. Embodiments of the cuff mayrelax relative to the subject's limb over time, thereby reducingpressure and eventually allowing reperfusion. This may be caused byvarious factors, including relaxation of muscles in the subject's limb,stretching of the cuff about the limb, air leaks (intentional orunintentional), and the like. To this end, a sensor may provide pressurereadings as feedback to the controller. The controller can measure anydifference between the set point and the actual pressure reading and canprovide any necessary commands to the actuator to compensate for errors.

Various approaches may be used to define an appropriate set point forthe controller during the ischemic duration. According to oneembodiment, the set point is manually entered into the treatmentprotocol by the doctor (or other medical professional). Alternately, thedoctor may select a set point in terms of the subject's systolic bloodpressure. In one embodiment, the set point may be selected as a fixedpressure amount over the subject's systolic blood pressure, such as 5 mmHg, 10 mm Hg, 15 mm Hg, 20 mm Hg, 25 mm Hg, 30 mm Hg, or any other fixedamount above systolic pressure of the subject. In other embodiments, theset point may be defined as a percentage of the subject's systolic bloodpressure, such as 102% of systolic, 105%, 110%, 115%, and otherpercentages, as aspects of the invention are not limited in thisrespect. The point above systolic pressure may be set by the medicalprofessional and may be dependent upon several factors including, butnot limited to the size of the subject, the size of the subject's limb,the subject's blood pressure, confirmation of blood flow cessation, andthe like.

The treatment protocol, according to some embodiments, includes phasesto identify the subject's systolic blood pressure. The cuff may beallowed to loosen about the subject's limb, from a point believed to beabove systolic pressure, in a systematic manner while sensors aremonitoring the limb for the onset of Korotkoff sounds or vibrations.Once the systolic pressure is identified, the treatment protocol maycontinue in the normal course.

Identification of systolic pressure may optionally occur at any timeduring a treatment protocol, or not at all. According to someembodiments, each treatment cycle begins with the identification of thesubject's systolic blood pressure. In other embodiments, systolicpressure may be identified only once during an initial portion of thetreatment protocol. In still other embodiments, systolic pressure may beidentified as the cuff is released during the cuff release portion ofeach treatment cycle. Still, as discuss herein, systolic pressure maynot be identified at all during a treatment protocol, as aspects or theinvention are not limited in this regard.

The system can be configured to adjust the pressure set point during theischemic duration. As discussed herein, the system may include sensorsthat detect the onset of reperfusion, such as may be indicated by thepresence of Korotkoff sounds or vibrations. The presence of Korotkoffsounds during an ischemic duration can indicate that either cuffpressure has fallen below systolic or that systolic pressure has risenabove the set point that was previously above systolic pressure. In sucha situation, the controller may adjust the set point based on the newlyidentified systolic pressure and/or other information and in thisregard, can identify and prevent unwanted reperfusion that mightotherwise occur.

The cuff release portion of a treatment cycle occurs at the end of theischemic duration and includes release of the cuff to a point belowdiastolic pressure. According to some embodiments, cuff releasecomprises releasing the pressure or tension of the cuff. In embodimentsthat utilize a pneumatic cuff, this may simply be associated with movingan air release valve to the fully open position to allow a rapidreduction in cuff pressure and a corresponding rapid relaxation of thecuff about the subject's limb. However, it is to be appreciated, that inother embodiments, that cuff relaxation may occur in a slower, morecontrolled manner, as aspects of the invention are not limited in thisrespect. Additionally, as discussed herein, the cuff release may beaccompanied by monitoring for the onset of Korotkoff sounds orvibrations to identify or confirm the systolic pressure of the subject.

The reperfusion duration follows the cuff release in embodiments of thetreatment cycle. Reperfusion through the limb is allowed for a period oftime termed the reperfusion duration. Much like the ischemic duration,reperfusion may be allowed for varied lengths of time, as short as afive seconds, one minute or more, and as long as 20 minutes, or evenlonger. The reperfusion duration may remain constant from treatmentcycle to treatment cycle during a common treatment protocol, or may varybetween each treatment cycle, as aspects of the invention are notlimited in this respect.

The treatment protocol may comprise any number of treatment cycles. Asdiscussed herein, a common treatment cycle may simply be repeated aplurality of times, such as two, three, four, or more times, to completea treatment protocol. Alternately, the treatment cycles of a treatmentprotocol may be programmed with different parameters, such as differentischemic durations, reperfusion durations, pressure set points duringthe ischemic duration, and the like.

In some embodiments, the system includes features to ensure subjectcompliance with a treatment regime. By way of example, embodiments mayinclude a data logging feature that records the system parameters, suchas cuff pressure or tension, during all phases of a treatment protocol.Date of time of operation may also be recorded. In this regard, a recordmay be kept of the actual use of the system so that a doctor can confirmthe extent of subject compliance. Other features, such as personalinformation to identify the patient, may also be recorded by the system.

Embodiments of the system may incorporate various features to inform thesubject or medical professional about the progress of the treatmentprotocol. Audible or visual indicators may accompany any of the phasesof the treatment protocol. By way of example, a clock may show eitherthe amount of time that has elapsed or that remains for a given portionof the treatment protocol or the entire protocol. Embodiments may alsoinclude other features to keep the subject and/or medical professionalinformed, as aspects of the invention are not limited in this regard.

According to some embodiments, the system includes features to preventtampering or accidental reprogramming by a subject. By way of example,in some embodiments, the reprogrammable features may only be accessedafter entering a code. This can prevent a subject from mistakenlyreprogramming the treatment protocol or otherwise interfering with theoperation of the system. It is to be appreciated that other devices mayalso be used to prevent accidental reprogramming, such as electronickeys, mechanical locks and the like.

The system may be configured for use is a variety of environments. Byway of example, the system may be mounted on a portable stand withcasters to facilitate easy movement about a healthcare facility, like ahospital. The stand may position the controller, user interface, andconnections to the cuff at a convenient height for the subject and/or adoctor or nurse who may be supervising the subject. In otherembodiments, the system is configured for portable use outside of amedical facility. In such embodiments, the system may be configured forready placement into a suitcase for easy transport. Still, otherembodiments may not be configured to be portable, as aspects of theinvention are not limited in this respect.

The system is also not limited to components illustrated in theembodiment of FIG. 1. by way of example, according to other embodiments,like that illustrated in FIG. 3, cuffs may be configured to constrict asubject's limb through alternative mechanisms. In the illustratedembodiment, the cuff is configured as a band having a ratchetingmechanism positioned at one end. In use, the band is wrapped about thelimb of a subject with the free end of the band passing through theratcheting mechanism. In such an embodiment, the actuator may comprise amechanism that pulls the free end of the band further through theratcheting mechanism to retract the cuff about the limb, or that freesthe ratcheting mechanism to release the band to, in turn, release theband from the limb. Still other mechanisms, such as tourniquetmechanisms, are possible, as aspects of the invention are not limited inthis respect.

As described above with reference to FIG. 3, some embodiments may have acuff that comprises a band that does not inflate, but rather istightened about a subject's limb by another mechanism. In suchembodiments, the actuator may comprise a tensioning mechanism configuredto move one end of the band relative to other portions of the band so asto place the band in tension. As shown, the mechanism can includeopposed rollers held in close proximity to one another within a housing.The housing includes a slot for receiving a free end of the band and afixation point for fixed attachment to the opposite end of the band. Thefree end of the band is passed into the slot and between the rollers.The rollers may be mechanically actuated to rotate relative to oneanother, such as by an electric motor, to pull the free end through thehousing and thus tighten the band around a subject's limb.

The tensioning mechanism may include opposed rollers mounted on aratcheting, free wheel mechanism. The freewheel mechanism allows theband to be pulled through the slot in one direction with minimalresistance so that the band may be pulled rapidly to a snug positionabout a subject's limb. The free wheel mechanism also prevents the bandfrom moving through the slot in the loosening direction, unless themechanism is released or the opposed rollers are actuated. It is to beappreciated that not all embodiments will include a free wheelmechanism, as aspects of the invention are not limited in this regard.

The opposed rollers rotate in either direction to tighten and loosen theband during use. When required, the rollers may rapidly rotate until theband achieves a particular tension. The rollers may further be actuatedto make minor adjustments to the tension in the band during use. Whenthe cuff is to be released from the subject's limb, a ratchetingmechanism or clutch may be released such that the opposed rollers areallowed to move freely, thus rapidly releasing tension.

Aspects of the invention are not limited to the embodiments of cuffsillustrated herein. By way of example, in some embodiments, the cuff maybe positioned in direct contact with the artery of a patient, such asthrough intraoperative placement.

Embodiments of the present invention may be useful whenever it isdesirable to prevent, inhibit altogether, or reduce the possibility orseverity of ischemic injury. Embodiments of the invention contemplateboth therapeutic and prophylactic treatment of subjects. The methods oftreatment disclosed herein can be used to reduce ischemic injury inorgans including but not limited to the heart, brain, kidney, pancreas,lung, intestine and the like. Further details regarding thephysiological mechanisms of remote ischemic preconditioning may be foundin the co-owned U.S. patent application entitled Anti-Ischaemic Agentfiled on Nov. 10, 2006 under express mail label number EV492322827USunder attorney docket number H0780.70000US00, which is herebyincorporated by reference in its entirety.

The foregoing written specification is considered to be sufficient toenable one ordinarily skilled in the art to practice the invention. Thepresent invention is not to be limited in scope by examples provided,since the examples are intended as mere illustrations of one or moreaspects of the invention. Other functionally equivalent embodiments areconsidered within the scope of the invention. Various modifications ofthe invention in addition to those shown and described herein willbecome apparent to those skilled in the art from the foregoingdescription. Each of the limitations of the invention can encompassvarious embodiments of the invention. It is, therefore, anticipated thateach of the limitations of the invention involving any one element orcombinations of elements can be included in each aspect of theinvention. This invention is not limited in its application to thedetails of construction and the arrangement of components set forth orillustrated in the drawings. The invention is capable of otherembodiments and of being practiced or of being carried out in variousways.

Also, the phraseology and terminology used herein is for the purpose ofdescription and should not be regarded as limiting. The use of“including”, “comprising”, or “having”, “containing”, “involving”, andvariations thereof herein, is meant to encompass the items listedthereafter and equivalents thereof as well as additional items.

1-22. (canceled)
 23. An automatic device for remote ischemicpreconditioning treatment, the device comprising: a cuff configured toretract about a limb of a subject, a controller detachably connected tosaid cuff, said controller being configured to periodically: inflatesaid cuff to a cuff pressure at or above a limb occlusion pressure ofthe subject, maintain said cuff pressure at or above said limb occlusionpressure for a period of at least about one minute, and deflate saidcuff, wherein said cuff is further configured to be retained about saidlimb and deliver said remote ischemic preconditioning treatment.
 24. Thedevice as in claim 23, wherein said controller is connected to an outerside of said cuff over said limb.
 25. The device as in claim 24, whereinsaid controller is connected to an inflatable portion of said cuff andoriented to face a user.
 26. The device as in claim 23, wherein saidcontroller is sufficiently powered for at least two remote ischemicpreconditioning treatments.
 27. An automatic device for remote ischemicpreconditioning treatment, the device comprising: a cuff configured toretract about a limb of a subject, a controller detachably connected toan outer side of said cuff over said limb, said controller beingconfigured to periodically: inflate said cuff to a cuff pressure at orabove a limb occlusion pressure of the subject, maintain said cuffpressure at or above said limb occlusion pressure for a period of atleast about one minute, and deflate said cuff, wherein after initialactivation by a user, said controller is further configured to conductand complete said entire treatment without further user input.
 28. Thedevice as in claim 27, wherein said initial activation is a single userinput.
 29. The device as in claim 27, wherein said controller is furtherconfigured for automatic hemodynamic surveillance of the subject duringsaid remote ischemic preconditioning treatment.
 30. The device as inclaim 29, wherein said hemodynamic surveillance is based on measuringpressure in said cuff.
 31. The device as in claim 30, wherein saidcontroller is further configured to detect systolic blood pressure ofsaid subject.
 32. The device as in claim 31, wherein said controller isfurther configured to detect systolic blood pressure of said subject atleast once during maintaining said cuff pressure at or above said limbocclusion pressure for said period of at least about one minute.
 33. Adevice for remote ischemic preconditioning, the device comprising: acuff sized to retract about a limb of a subject, a controller connectedto said cuff, said controller configured to inflate and deflate saidcuff according to a remote ischemic preconditioning treatment protocol,said treatment protocol including a plurality of treatment cycles, eachof said treatment cycles comprising: inflating said cuff to a cuffpressure at or above a limb occlusion pressure of the subject,maintaining said cuff pressure at or above said limb occlusion pressurefor a period of at least about one minute, and deflating said cuff,wherein during maintaining said cuff pressure at or above said limbocclusion pressure, said controller is further configured to vary saidcuff pressure above said limb occlusion pressure at least once during atleast one of said treatment cycles.
 34. The device as in claim 33,wherein said controller is further configured to detect a systolic bloodpressure of the subject during varying of said cuff pressure.
 35. Thedevice as in claim 34, wherein said controller is further configured toinflate said cuff pressure at or above a previously recorded systolicblood pressure during varying of said cuff pressure.
 36. The device asin claim 35, wherein said controller is further configured to determinea diastolic pressure of the subject, whereby said subject is undercontinuous hemodynamic surveillance throughout said ischemicpreconditioning treatment.